Drug Evaluation Committee 2022-12 Handling of SAE reports for hospitalization for planned surgery (Part 4)
Related classification: Adverse drug reaction reports
Date of first publication: Sep 2022
Question
I would like to ask a question regarding Clinical Trial 119, Questions and Opinions.In the example given in "2008-03 Handling of SAE Reporting for Scheduled Hospitalization for Surgery (Part 2)," it is stated that polypectomy need not be judged as serious until the fact that the patient is hospitalized. However, in my experience alone, there are a large number of CRCs who think that "as long as a scheduled hospitalization is scheduled in any case, it does not need to be considered as a serious illness.
In such cases, for example, even if the event is clearly related to survival or prognosis of the disease without surgery, if the hospitalization is "scheduled" for some time in the future due to the availability of operating rooms, the effects of corona, or the patient's schedule, it is not considered to be serious. In some situations, it may be determined that a disease for which surgery is scheduled after the trial is over (end of follow-up period) is not serious, and the trial is terminated as non-serious.
In addition, according to the opinion of the Pharmaceutical Manufacturers Association in response to the same question, "The sponsor needs to collect information as promptly as possible in order to determine whether the event should be reported urgently (e.g., whether it was caused by deterioration during the clinical trial)," but there are cases where it is determined that the event is not an SAE but is reported because the sponsor requests it. However, there are cases where it is determined that a report is made because it is requested, although it is not an SAE. For the same reason, we have also experienced a CRC decision not to treat an event that occurred in a clinical trial as serious even if there were measures/treatments that would have been performed during hospitalization, because there was no actual extension of hospitalization for the subject who was originally hospitalized for a long period of time.
Article 273 of the Pharmaceutical Affairs Law states that "...hospitalization or prolongation of hospital stay is required." This premise remains true under any circumstances, and I believe that an event that is "required" should be considered serious.
I am very troubled by the fact that there are so many conflicting views of the sponsor and CRC on this matter, so I would greatly appreciate it if you could add your views to the Clinical Trial 119 Opinion. As for the polypectomy in 2008-03, I understand that it may not necessarily be judged as serious at that time from the viewpoint of necessity/urgency, as you have stated.
Pharmaceutical Association's Opinion
The "Q&A on Post-Marketing Adverse Reaction Reports and Clinical Trial Adverse Reaction Reports in Response to the E2B(R3) Implementation Guide" (June 24, 2022, Ministry of Health, Labour and Welfare, Pharmaceuticals and Welfare Bureau, Drug Evaluation and Administration Division and Drug Safety Division) states the following. Q39: [Post-marketing] Enforcement action: The drug is considered to be a serious adverse event if it results in hospitalization or prolongation of hospitalization.Q39: [Post-marketing] How do you define "cases that require hospitalization or prolonged hospitalization at a hospital or clinic for treatment" in Article 228-20 of the Enforcement Regulations?
A39: [Post-marketing] "Cases that require hospitalization or prolonged hospitalization for treatment" in the ICH regulations (see E2D Guidelines) falls under this category. A39: "Cases that require hospitalization or an extended period of hospitalization for treatment of adverse drug reactions." This also applies to cases where the patient is hospitalized for treatment of adverse drug reactions but no specific treatment is performed (bed rest treatment). (Omitted below.) On the other hand, in the case of a subject who is hospitalized.
On the other hand, if a subject is hospitalized and a new adverse event occurs, even if the originally planned length of hospitalization is not extended, the applicability of the event to a serious adverse event should be determined by considering whether the measures/treatment for the event were originally performed in the hospital or not, and whether the event meets other criteria for a serious adverse event. The investigational new drug is not considered to be a serious adverse event.
In some cases, the clinical trial protocol may specify the scope of serious adverse events according to the characteristics of the investigational drug, or may specify the reporting of serious adverse events to the sponsor after the follow-up period. In such cases, it is necessary to provide the information to the sponsor and discuss and agree on the handling of the information.